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The Effect Of Thymosin Alpha 1 On Expression Of Signal Transduction Molecules In Lymphocytes

Posted on:2002-11-04Degree:DoctorType:Dissertation
Country:ChinaCandidate:H H ZhuFull Text:PDF
GTID:1104360032950157Subject:Internal medicine
Abstract/Summary:PDF Full Text Request
Thymus is one of human central immune organ, which plays an important role in inducing T lymphocytes differentiation and maturation. Thymus also plays main role in the development of peripheral immune organ. So that thymus acts on an important role in the development of lymph system and maintain normal immune function. In recent years some people pointed out that thymus also has a role on nerve-endocrine system. From human puberty, thymus began to atrophy physically and the incidence of tumor, infection and immune deficient diseases increase gradually. A lot of investigations indicated that extract of calf thymus can be used to treat tumor, infection diseases and other diseases caused by the fall of thymus.Thymic epithelial cells may secrete many thymic hormones such as thymosin, thytnopoietin, thymic humoral factor, lymphocytic stimulator, serum thymic factor and so on. They are the main component of thymic microenvironment, and play important role on T lymphocyte differentiation and regulation T cell function. Recently thymic hormone was purified into several components. Thymosin alphal (Ta 1) is one of thymic hormone, which is composed by 28 amino acid'and was first isolated by Goldstein et al. T a 1 has immunoregulating function. It can facilitate sensitized lymphocytes to secrete cytokines such as IFN- a ,IFN- Y, IL-2 in vitro. It can also enhance the expression of cytokine receptor with high affinity, regulate the TdT activity of marrow precusor cells and splenocytes, enhance surface antigen Thy 1 and Lytl,2,3 expression on surface of marrow precusor cells, facilitate the growth of NK cell and enhance its activity, by enhancing T helper cell function to facilitate allo/auto lymphocytes reaction, inhibit apoptosis in process of thymocyte maturation. The results of using T a 1 in vivo also indicated that T a l play important role in T celldevelopment and reconstitute its function. It can promote lymphocytes to secrete IL-2 and to express IL-2 receptor, enhance the ability of anti-infection and clean up virus in vivo, enhance immune function, anti-oxidation and inhibit growth of tumor cells. So that T a 1 plays important role on enhancing host immune function .cleaning up virus and against tumor.Clinically, T a 1 is used to assist the treatment of chronic virus infection such as HBV and HCV infection, tumor such as melanoma, lung cancer, leukemia, squamous epithelial cell carcinoma, colon carcinoma , and immune deficiency patients and took good results. T a 1 can also used as vaccine adjuvant. Study of its mechanism will be osculated with its application on infectious diseases, oncology and immunologic diseases.At present, the study of T a ?l mainly focus on its biologic function and application ,which have make a great progress. But the study covering its mechanism is seldom reported.Firstly, T a 1 receptor is still not be cloned now and we also have little know about it. Only some results showed that Ta 1 can bind with some structure on cell surface. Garaci et al reported that T a 1 receptor with high affinity exist on surface of mice lymphocytes by using immunoflurescent assay. Moody et al found that T a 1 can bind with VIP (vasoactive intestinal peptide) receptor in low affinity (IC50=10 P M), but T a 1 is not an antagonist of VIP receptor, which suggested that other signal accept molecule was exist. The above results at least indicated that an molecule, such as T a 1 binding protein, which can binding T?1 is exist. The elucidation of the To 1 binding protein, which is interacted with T a 1 directly when it exerting its biological function, will make great effect on studying the receptor, mechanisms and function of T a 1 in advance.Secondly, the reports related to the change of signal transduction molecule caused by T a 1 is little. Although some progress have been made in study on second messenger after T a 1 stimulation, we still do not know which molecule firstly recognize Ta land which molecules participated in signal transduction and the changes cause by them.In this research...
Keywords/Search Tags:Thymosin alpha 1, Yeast two-hybrid system, T Lymphocyte, cDNA library, Thymosin alpha 1-binding protein, Actin-gamma, Elongation factor-1 alpha
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